EPILEPSY affects 5–10‰ of the general population.

It is due to sudden, excessive depolarization of

some or all cerebral neurons. This may be:

• localized (focal or partial seizure);

• spread to cause a secondary generalized seizure;
• may affect all cortical neurons simultaneously
(primary generalized seizure).
EEG

Cortex:
F – frontal
O – occipital
T – temporal

Rang et al.
Pharmacology
– 5th Ed. (2003)

Classification of seizures
HISTORY

• Bromides (1857)
• Phenobarbital (1912)
• Phenytoin (1938)
• Later: Ethosiximide, Carbmazepine
• New anticonvulsants (in the last 15–20 years):
vigabatrin, gabapentin, lamotrigine, topiramate,
oxcarbazepine, levetiracetam, pregabalin etc.
 1. Carboxamides (enzyme inductors – CYP450):
Carbamazepine (+ neuropathic pain – n. trigeminus,
postherpetic pain, etc.), Oxcarbazepine
2. Hydantoins: Phenytoin (enzyme inductor), used in digitalis
ANTISEIZURE DRUGS

intoxication too
3. Barbiturates (Phenobarbital – enzyme inductors) and their
analogues (Primidone – prodrug)
4. Succinimides: Ethosuximide (casp. 250 mg – petit mal)
5. Valproates (enzyme inhibitors): Sodium valproate (Depakin®)
6. Benzodiazepines: Clonazepam, Clorazepate, Diazepam
t1/2 43 h, amp. 10 mg/2 ml i.m./i.v., Lorazepam, Nitrazepam
7. GABA analogues: Gabapentin, Tiagabine
8. Hetereogenic anticonvulsants: Lamotrigine, Levetiracetam,
Pregabalin (partial seizures, peripheral neuropathic pain),
Topiramate, Vigabatrin
MECHANISM OF ACTION OF ANTIEPILEPTIC DRUGS
Antiepileptics inhibit the neuronal discharge or its spread in one or
more of the following ways:
(1) Enhancing GABA synaptic transmission: barbiturates, benzo-
diazepines, gabapentin; the result is increased permeability to chloride
ion, which reduces neuronal excitability.
(2) Reducing cell membrane permeability to voltage-dependent
sodium channels: carbamazepine, lamotrigine, phenytoin, valproate.
(3) Reducing cell membrane permeability to calcium T-channels:
valproate, ethosuximide; the result is diminishing of the generation
of action potential.
(4) Inhibiting excitory neurotransmitter glutamate: lamotrigine.
 GABA
Barbiturates
Benzodiazepines
Gabapentin
Levetiracetam
Tiagabine
Topiramate
Valproate
Vigabatrin

Na+ Ca2+
Carbamazepine
Ethosuximide
Lamotrigine
Levetiracetam
Oxcarbazepine
Pregabalin
Phenytoin
Valproate
Topiramate
Valproate
 PHENYTOIN
• Effects –
- Antiseizure with no sedative effect
- Seizure modifying action
▼PHENYTOIN
ARS: IMPAIRMENT OF COGNITIVE FUNCTION
HIRSUTISM
SKIN RASHES (MORBILLIFORM RASH)
STEVEN – JOHNSON SYNDROME
GUM HYPERPLASIA (DUE TO THE INHIBITION OF
COLLAGEN METABOLISM),
HYPERGLYCEMIA
ANAEMIA
OSTEOMALACIA.
▼CARBAMAZEPINE
Carbamazepine is a drug of first choice for partial and tonic
clonic seizures but aggravates myoclonic and absence seizure.
Antipsychotic agent and antidiuretic
Adverse reactions (ARs):
blurring of vision, diplopia,
drowsiness, vertigo, ataxia
depression of AV conduction
skin rashes
liver and kidney dysfunction
water retention
teratogenic
▼VALPROIC ACID (Sodium valproate)
Discovered serendipitously
beneficial against wide variety of seizures
ARs can be troublesome:
teratogenicity,
loss of hair which grows back curly.
Nausea
liver failure (under 10 years)
▼BENZODIAZEPINES
•Diazepam
Antiseizure, antianxietic
Effects - hypnosis, decreased anxiety, muscle relaxation,
anterograde amnesia, and anticonvulsant activity
Slight reduction of resp. drive
Increase Adenosine – Cardiac depressant – negative inotrope

ADR – tolerance, Ataxia

▼LAMOTRIGINE (t1/2 6–24 h) inhibits excitory neurotransmitter
glutamate. Lamotrigine is effective for the treatment of partial and
secondarily generalized tonic-clonic seizure. It is generally well
tolerated but may cause serious ARs of the skin, including
Stevens–Johnson syndrome and toxic epidermal necrolysis.

▼TOPIRAMATE (t1/2 21 h) is used as adjunctive treatment for

partial seizure, with or without secondary generalization. ARs:
sedation, weight loss, acute myopia, raised intraocular pressure.

▼ETHOSUXIMIDE (t1/2 55 h) blocks T-type calcium ion

channels. It is active in absence seizures (petit mal).
ARs: gastric upset, CNS effects and allergic reactions.
MAIN INDICATIONS OF ANTIEPILEPTIC DRUGS
Anticonvulsive drugs of choice
Grand mal: I choice – valproate or Lamotrigine
Alternative – Carbamazepine, Topiramate or Phenytoin

Petit mal: I choice – Ethosuximide or valproate

Alternative – Clonazepam or Lamotrigine
Partial seizures: I choice – Carbamazepine or
valproate
Alternative – Phenytoin, Lamotrigine, Vigabatrin, Topiramate

Status epilepticus: I choice – Diazepam or Lorazepam (i.v.)

Alternative – Phenobarbital (i.m./i/v.)
Treatment of status epilepticus in adults

Patient in opisthotonus (grand mal)

TRIGEMINAL NEURALGIA, POSTHERPETIC PAINS,
ETC.
FEBRILE CONVULSION AND POST-TRAUMATIC
EPILEPSY
GENERAL GUIDE TO ANTIEPILEPSY PHARMACOTHERAPY

(1) The decision whether or not to initiate drug therapy after a

single seizure remains controversial since approximately 25%
of patients may not have another seizure.
(2) Therapy should start with a single drug (70% of patients can
be controlled on one drug (monotherapy).
(3) Anticonvulsant drug therapy should be appropriate to the type
of seizure.
(4) If the attempt to control epilepsy by use of a single drug is
unsuccessful, it should be withdrawn and replaced by a second
line drug, though these are effective in only 10% of patients.
(6) Effective therapy must never be stopped suddenly,
only gradually.
(7) After a period of at least 2–3 years free from seizures, with-
drawal of anticonvulsants can be considered.